3种不同溶媒介质脂质体的制备及其初步稳定性考察

Study on the Preparation and Preliminary Stability of Three Liposomes with Different Solvent Medium

目的:制备3种不同溶媒介质脂质体,即普通脂质体、乙醇脂质体、丙二醇脂质体,筛选及优化制备工艺,并初步考察其稳定性。方法:以薄膜分散法制备普通脂质体,注入法制备乙醇脂质体和丙二醇脂质体。在相同的处方组成下,考察水化时间、水浴温度、旋转速度等因素对普通脂质体粒径分布的影响,醇水比例、搅拌速度、过膜方式等因素对乙醇脂质体和丙二醇脂质体粒径分布的影响,在此基础上运用正交设计对制备工艺进行优化。以3种不同溶媒介质脂质体的外观形态及平均粒径的变化为指标,分别于第0,1,15,30天取样评价其稳定性。结果:正交试验结果表明,薄膜分散法制备普通脂质体的最佳工艺条件为:水化时间60 min,水浴温度50℃,旋转速度200 r·min^(-1)。注入法制备乙醇脂质体和丙二醇脂质体的最佳工艺条件为:醇水比例1∶2,搅拌速度1 000 r·min^(-1),先0.45μm后0.22μm微孔滤膜的过膜方式。最佳工艺条件制备得到的3种脂质体均为封闭的单层囊状或多层圆球体,普通脂质体平均粒径(1 016.2±135.6)nm,乙醇脂质体平均粒径(578.7±89.2)nm,丙二醇脂质体平均粒径(351.4±53.8)nm。3种脂质体在30 d的观察期内都不稳定,放置15 d后出现明显的分层现象。结论:优化的最佳工艺制得3种不同溶媒介质脂质体粒径均为微纳米级,但稳定性较差,宜临用前配制。

Objective： To prepare three kinds of liposomes with different solvent medium named common liposomes, ethanol liposomes and propylene glycol liposomes, screen and optimize the preparation process, and investigate the stability preliminarily. Methods： Common liposomes were prepared by a thin film dispersion method, and ethanol liposomes and propylene glycol liposomes were prepared by an injection method. With the same formula compositions, the size distribution of common liposomes was studied with hydration time, water bath temperature and rotation speed. The size distribution of ethanol liposomes and propylene glycol liposomes was studied different volume ratio of alcohol to water, stirring speed and mode of membrane passmg. An orthogonal design was adopted to obtain the optimal preparation technology based on the influences. Preliminary stability of the three different solvent medium liposomes was evaluated respectively on 0, 1st, 15th and 30th day using the changes of morphology and the mean particle size as the indicators. Results： The results of orthogonal test showed that the best preparation method for common liposomes was as follows： the hydration time was 60 rain, the water bath temperature was 50℃ and the rotation speed was 200 r ·min-1. The best preparation method for ethanol liposomes and propylene glycol liposomes was as follows： the volume ratio of alcohol to water was 1 ：2, the stirring speed was 1 000 r· min-1 and the mode of membrane passing was 0.45 μm at first and then changed to 0.22 μm. Under the optimum preparation conditions, the three liposomes were closed monolayer or muhilayer cystic spherosomes. The average diameter of common liposomes, ethanol liposomes and propylene glycol liposome was （1 016.2 ± 135.6）, （578.7 ± 89.2） and （351.4 ± 53.8） nm, respectively. All the three liposomes were unstable during the one-month observation period. After the 15-day storage, obvious delamination appeared. Conclusion： Three different solvent medium liposomes prepared with the best process are in micro-scale or nano-scale. They are in poor stability, which should be freshly prepared before use.